Supplementary material
Experimental details and spectroscopic characterization for the synthesis of 11-cis7-methylretinal
(2E,4E)-5-Iodo-3-methylhexa-2,4-dien-1-ol
5.
To
a
solution
of
(2E,4E)-5-
tributylstannyl-3-methylhexa-2,4-dien-1-ol (0.193 g, 0.481 mmol) in CH2Cl2 (7.3 mL)
was added a solution of I2 (0.122 g, 0.481 mmol). The mixture was diluted with CH2Cl2
(5 mL) and washed with aqueous Na2S2O3 (3x). The organic layer was dried (Na2SO4)
and the solvent was evaporated. The residue was purified by column chromatography
(silica gel, 90:10 hexane/ethyl acetate) to afford 0.113 g (99%) of a yellow oil identified
as (2E,4E)-5-iodo-3-methylhexa-2,4-dien-1-ol 5. 1H-NMR (400.16 MHz, C6D6):  6.58
(s, 1H, H4), 5.23 (t, J = 6.6 Hz, 1H, H2), 3.76 (d, J = 6.6 Hz, 2H, 2H1), 2.29 (s, 3H, C5CH3), 1.30 (s, 3H, C5-CH3).
13C-NMR
(100.63 MHz, C6D6):  144.5 (d), 135.0 (s),
131.1 (d), 97.9 (s), 59.4 (t), 29.8 (q), 16.6 (q) ppm. MS (EI+): m/z (%) 238 (M+, 41), 128
(10), 127 (24), 111 (100), 96 (11), 95 (21), 93 (48), 91 (37), 83 (17), 79 (22), 77 (44), 67
(18), 65 (16). HRMS (EI+): Calcd. for C7H11IO, 237.9855; found, 237.9848. FTIR
(NaCl):  3550-3050 (br, OH), 2918 (s, C-H), 2853 (m, C-H), 1435, 1377 cm-1.
(2E,4E)-3-Methyl-5-(2,6,6-trimethylcyclohex-1-en-1-yl)hexa-2,4-dien-1-ol 6. To a
solution of (2E,4E)-5-iodo-3-methylhexa-2,4-dien-1-ol 5 (0.119 g, 0.5 mmol) in THF (3
mL) was added Pd(PPh3)4 (57.4 mg, 0.05 mmol). After stirring for 5 min (2,6,6trimethylcyclohex-1-en-1-yl)boronic acid 3 (0.105 g, 0.63 mmol) was added. After
addition of a 10% aqueous TlOH solution (4.81 mL, 1.90 mmol), the mixture was
stirred for 17h at 25 °C. The reaction mixture was diluted with t-BuOMe (3 mL) and
washed with brine (3x). The organic layer was dried (Na2SO4) and the solvent was
evaporated. The residue was purified by column chromatography (silica gel, 90:7:3
1
hexane/ethyl acetate/Et3N) to afford 81 mg (70%) of a yellow oil identified as (2E,4E)3-methyl-5-(2,6,6-trimethylcyclohex-1-en-1-yl)hexa-2,4-dien-1-ol 6. 1H-NMR (400.16
MHz, CDCl3):  5.52 (t, J = 6.9 Hz, 1H, H2), 5.44 (s, 1H, H4), 4.25 (d, J = 6.9 Hz, 2H,
2H1), 1.9-1.8 (m, 2H, 2H3’), 1.85 (s, 3H, CH3), 1.79 (s, 3H, CH3), 1.8-1.6 (m, 2H, 2H4’),
1.51 (s, 3H C2’-CH3), 1.5-1.4 (m, 2H, 2H5’), 0.99 (s, 6H, C6’-(CH3)2). 13C-NMR (100.63
MHz, CDCl3):  144.1 (s), 137.5 (s), 136.8 (s), 131.9 (d), 127.3 (d), 126.3 (s), 59.9 (t),
40.1 (t), 34.9 (s), 32.1 (t), 30.1 (q), 28.8 (q), 21.3 (q), 21.0 (q), 19.7 (t), 17.7 (q) ppm.
MS (EI+): m/z (%) 234 (M+, 27), 203 (20), 173 (12), 159 (17),149 (12), 147 (28), 145
(26), 135 (13), 134 (17), 133 (100), 121 (24), 119 (49), 107 (15), 105 (17), 95 (14), 91
(20), 83 (26), 81 (16), 69 (31). HRMS (EI+): Calcd. for C16H26O, 234.1984; found,
234.1980. FTIR (NaCl):  3500-3100 (br, OH), 2926 (s, C-H), 1458, 1374 cm-1. UV
(MeOH): max 238 nm.
(2E,4E)-3-Methyl-5-(2,6,6-trimethylcyclohex-1-en-1-yl)hexa-2,4-dien-1-al 7. To a
cooled (0 °C) stirred solution of N-methylmorpholine N-oxide (78 mg, 0.65 mmol) in
CH2Cl2 (2.6 mL) containing 4Å Molecular Sieves was added a solution of (2E,4E)-3methyl-5-(2,6,6-trimethylcyclohex-1-en-1-yl)hexa-2,4-dien-1-ol 6 (101.4 mg, 0.43
mmol) in CH2Cl2 (1.3 mL). After stirring for 10 min, TPAP (7.8 mg, 0.022 mmol) was
added and the mixture was stirred at 25 °C for 4.5 h. The mixture was diluted with
CH2Cl2 (5 mL) and washed with aqueous Na2SO3 (3x). The organic layer was dried
(Na2SO4) and the solvent was evaporated. The residue was purified by column
chromatography (silica gel, 93:5:2 hexane/ethyl acetate/Et3N) to afford 68.4 mg (68%)
of a yellow solid identified as (2E,4E)-3-methyl-5-(2,6,6-trimethylcyclohex-1-en-1yl)hexa-2,4-dienal 7. M.p.: 66-68 °C (Et2O). 1H-NMR (400.16 MHz, (CD3)2CO): 
10.16 (d, J = 7.9 Hz, 1H, H1), 5.94 (d, J = 7.9 Hz, 1H, H2), 5.74 (s, 1H, H4), 2.39 (s, 3H,
2
CH3), 2.1-2.0 (m, 2H, 2H3’), 2.05 (s, 3H, CH3), 1.7-1.6 (m, 2H, 2H4’), 1.61 (s, 3H, C2’CH3), 1.6-1.5 (m, 2H, 2H5’), 1.10 (s, 6H, C6’-(CH3)2).
13C-NMR
(100.63 MHz,
(CD3)2CO):  191.8 (d), 157.0 (s), 145.4 (s), 144.8 (s), 131.5 (d), 129.9 (d), 127.4 (s),
40.8 (t), 35.6 (s), 32.6 (t), 30.4 (q), 29.7 (q), 22.6 (q), 21.3 (q), 20.3 (t), 18.8 (q). MS
(EI+): m/z (%) 232 (M+, 15), 217 (38), 203 (26), 161 (28), 150 (10),149 (20), 147 (28),
135 (13), 134 (24), 133 (100), 121 (18), 119 (47), 109 (37), 107 (16), 105 (22), 93 (12),
91 (27), 83 (15), 79 (15), 77 (18), 69 (14). HRMS (EI+): Calcd. for C16H24O, 232.1827;
found, 232.1824. FTIR (NaCl):  2927 (s, C-H), 1669 (s, C=O), 1605, 1441, 1374,
1201, 1126 cm-1. UV (MeOH): max 295 nm. Elemental analysis: Calcd. for C16H24O:
C, 82.7; H, 10.41; found: C, 82.1; H, 10.47.
11-cis-7-methyl-retinal 2. To a cooled (-78 ºC) suspension of (4-hydroxy-2-methylbut-2-enyl)-triphenylphosphonium bromide 8 (161.0 mg, 0.377 mmol) in THF (1 mL)
was added KHMDS (1.61 mL, 0.5M in toluene, 0.804 mmol). After stirring for 10 min
at -78 °C and 1h at 25 °C, the mixture was cooled to –78 ºC and a solution of (2E,4E)-3methyl-5-(2,6,6-trimethylcyclohex-1-en-1-yl)hexa-2,4-dien-1-al 7 (58.4 mg, 0.251
mmol) in THF (1 mL) was added. The resulting mixture was stirred for 30 min at -78
°C and 1h at 25 °C. The mixture was poured over H2O and extracted with Et2O (4x).
The combined organic layers were dried (Na2SO4) and the solvent was evaporated. The
residue was purified by column chromatography (82:15:3 hexane/ethyl acetate/Et3N) to
afford a yellow oil which was used immediately.
To a solution of this compound in CH2Cl2 (1.5 mL) was added MnO2 (0.393 g, 4.52
mmol) and Na2CO3 (0.479 g, 4.52 mmol), and the suspension was stirred at room
temperature for 1.5 h. The mixture was filtered through Celite and the solvent was
removed. The residue was purified by HPLC to afford 19.5 mg (26%) of a yellow oil
3
identified as 11-cis-7-methylretinal 2. 1H-NMR (400.16 MHz, C6D6):  9.93 (d, J = 7.6
Hz, 1H, H15), 6.62 (d, J = 12.0 Hz, 1H, H10), 6.37 (t, J = 11.9 Hz, 1H, H11), 6.15 (d, J =
7.6 Hz, 1H, H14), 5.68 (s, 1H, H8), 5.61 (d, J = 11.8 Hz, 1H, H12), 1.95 (s, 3H, CH3),
1.9-1.8 (m, 2H, 2H4), 1.77 (s, 3H, CH3), 1.75 (s, 3H, CH3), 1.6-1.5 (m, 2H, 2H3), 1.55
(s, 3H, CH3), 1.5-1.4 (m, 2H, 2H2), 1.1-1.0 (s, br, 6H, C1-(CH3)2). MS (EI+): m/z (%)
298 (M+, 47), 283 (24), 273 (31), 272 (100), 257 (48), 190 (49), 189 (32), 187 (36), 175
(53), 173 (55), 159 (66), 157 (33), 147 (33), 145 (48), 133 (52), 119 (44), 105 (31), 95
(34), 91 (37), 83 (28), 81 (29), 69 (44). HRMS (EI+): Calcd. for C21H30O, 298.2297;
found, 298.2304. UV (MeOH): max 368 ( = 19300), 257 nm.
4